Prostate cancer treatment just got a major boost from the PACE trials, which may have established a new standard of care in low- and favorable intermediate-risk disease, according to data presented at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting.¹

The results of the phase III PACE-B international randomized controlled trial showed that ultrahypofractionated radiation therapy delivered using stereotactic body technique is a noninferior treatment option for localized prostate cancer compared with conventionally fractionated radiotherapy. The unadjusted hazard radio favored treatment with fewer, higher doses of radiation vs conventional methods (hazard ratio = 0.73; P = .004). The 5-year event-free survival rates with stereotactic body radiation therapy and conventional fractionation were 95.8% and 94.6%, respectively. Authors of the study emphasized that these significant findings add weight to previous results from the associated PACE-A study—which compared stereotactic body radiotherapy to surgery for localized prostate cancer—and may reshape conventional treatment plans.

Nicholas van As, MD

“The outcomes for patients in both study arms were better than we expected,” said principal trial investigator Nicholas van As, MD, a consultant clinical oncologist, Medical Director of The Royal Marsden NHS Foundation Trust, and Professor at the Institute of Cancer Research, London. “To be able to sit with a patient and say, ‘We can treat you with a low-toxicity treatment in 5 days, and your chance of keeping the cancer at bay for 5 years is 96%,’ it’s a positive conversation to have.”

As Prof. van As reported, prostate cancer treatment has historically been dominated by conventional radiotherapy or surgery, often leading to significant side effects such as urinary incontinence or sexual dysfunction. Despite the effectiveness of these treatments, he added, it is important to provide care that balances treatment efficacy with quality of life.

The PACE studies aimed to address these concerns in intermediate-risk prostate cancer by using stereotactic body radiation therapy, which shrinks or destroys tumors with fewer, higher doses of radiation delivered in a small number of outpatient sessions. As Prof. van As explained, this approach uses advanced imaging and treatment planning techniques to deliver radiation with pinpoint accuracy, minimizing damage to surrounding healthy tissue.Patients who choose radiation therapy for intermediate-risk prostate cancer typically receive treatment in 20 to 40 daily fractions, whereas stereotactic body radiation therapy is typically given in 5 or fewer outpatient treatment sessions.

PACE-B Details

In PACE-B, stereotactic body radiation was compared with conventional radiation in patients with intermediate-risk, localized prostate cancer (T1C–T2C, Gleason scores ≤ 3+4). Noninferiority was measured by whether patients remained free of biochemical clinical failure, defined as an increase in prostate-specific antigen levels, distant metastases (or other evidence of recurrence), or death from prostate cancer. Prof. van As and colleagues enrolled 874 people who preferred radiation treatment or were unsuitable for surgery across 38 centers in the UK and Canada. The median patient age was 69.8 years.

Patients were randomly assigned to receive either stereotactic body radiation therapy (n = 443), consisting of five fractions over 1 to 2 weeks (36.25 Gy total dose), or standard fractionation radiation (n = 441), consisting of 39 fractions over 7.5 weeks (78 Gy) or 20 fractions over 4 weeks (62 Gy). None of the patients received androgen-deprivation therapy. Median follow-up was 73.1 months.

Disease Control Rates Exceed Expectations

As Prof. van As reported, biochemical clinical failure rates, the study’s primary endpoint, demonstrated effectiveness in both treatment arms, with 5-year event-free survival rates of 95.8% and 94.6% with stereotactic body radiation therapy and conventional fractionation, respectively (P = .007).

Although Prof. van As expected stereotactic body radiation to be noninferior to conventional fractionation, he was surprised at the level of disease control that both approaches were able to demonstrate. He attributed the high rates to improvements in image guidance and technologies to deliver radiation in recent years.

“One of the things this study demonstrated is that outcomes of high-quality radiation therapy are outstanding,” said Prof. van As. “We’ve become much more precise at tracking and reaching the targets. We’re able to put high doses of radiation in the right place and avoid putting high doses in areas we don’t want it.”

Safety Profile and Adverse Events

Investigators reported that side effects were low in both groups and did not significantly differ between treatment arms. Patients randomly assigned to receive stereotactic body radiation experienced an increase in genitourinary toxicity at the 2-year mark, said Prof. van As, but by 5 years, toxicity profiles for both treatment groups had leveled off.

At 5 years after treatment, 5.5% of patients given stereotactic body radiation experienced grade 2 or higher side effects affecting the genital or urinary organs vs 3.2% of those given conventional radiotherapy (P = .14). One person in each arm of the study experienced grade 2 or higher gastrointestinal side effects (P = .99).

According to Prof. van As, these findings highlight the need for surgeons to discuss these data with patients who have intermediate-risk prostate before opting for traditional prostatectomy, offering a potentially less impactful treatment option. “These results confirm with confidence that stereotactic body radiation therapy is noninferior to conventional fractionation,” he commented.

The PACE-C trial, which has completed accrual, is investigating stereotactic body radiation therapy in patients with intermediate- and high-risk prostate cancer who are also being treated with hormone therapy. 

DISCLOSURE: The PACE-B trial was funded by Accuray. Prof. van As has received research grants from Accuray and Varian and consultant fees from Accuray.

REFERENCE

1. van As N, Tree A, Patel J, et al: 5-year outcomes from PACE-B: An international phase III randomized controlled trial comparing stereotactic body radiotherapy vs conventionally fractionated or moderately hypofractionated external beam radiotherapy for localised prostate cancer. 2023 ASTRO Annual Meeting. Abstract LBA 03. Presented October 2, 2023.